Cell-cell interactions are critical for the establishment of proper tissue architecture during organ formation and for tissue maintenance in the adult. The failure of a cell to make and maintain appropriate contacts can result in birth defects, tumor formation and metastasis, and infertility in the case of gonad defects. The Drosophila gonad provides an excellent system for studying how cell-cell interactions regulate organogenesis. During embryonic development, germ cells (GCs) interact with somatic gonadal precursors (SGPs), forming a gonad with a defined architecture. SGPs form extensions that surround, or ensheath, each GC. GC ensheathment is likely to promote proper regulation of GC development by the SGPs, and GC development is severely affected when GC ensheathment does not occur. Recently, our lab conducted a large-scale genetic screen to identify new genes required for gonad formation, providing an important resource for uncovering the molecular mechanisms that regulate this process. Specifically of interest are two complementation groups that exhibit GC ensheathment defects;one that maps to the previously identified gene raw, and another that we are currently mapping, which we call unwrapped (unw). The ensheathment phenotype of raw and unw mutants is very similar to that previously observed for other genes required for ensheathment, suggesting these genes may function in a common pathway to regulate germline-soma interactions. The studies proposed here will (1) examine the changes in cell behavior that drive germline-soma interactions using single cell labeling and live imaging, and (2) elucidate further the cellular and molecular mechanisms by which raw and unw control germline-soma interactions in the gonad, and how these genes function relative to each other. This work will increase understanding of the mechanisms regulating cell-cell interactions during normal development, and how defects in these processes can lead to disease. Relevance to public health: A failure to establish proper cell-cell interactions during organ formation can result in birth defects or impaired organ function in adults, and such defects in the gonad can lead to infertility. In addition, cell-cell interactions control cell proliferation, and can result in tumor formation and metastasis when defective. The genes identified in these studies will increase our understanding of the mechanisms regulating cell-cell interactions, and provide potential therapeutic targets for diseases arising from defects in cell-cell interactions.